文献类型：期刊文献

英文题名：The potential treatment of N-acetylcysteine as an antioxidant in the radiation-induced heart disease

作者：Li, Yan-Ling[1,2];Wang, Gang[3];Wang, Bo-Wen[1,2];Li, Yong-Hong[4];Ma, Yong-Xia[5];Huang, Yuan[6];Yan, Wen-Ting[6];Xie, Ping[1,2,3]

第一作者：Li, Yan-Ling;李亚隆;李亚玲;李玉兰

通信作者：Xie, P[1];Xie, P[2];Xie, P[3]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou 730000, Peoples R China;[2]Gansu Prov Hosp, Dept Cardiovasc Med, 204 Donggang West Rd, Lanzhou 730000, Peoples R China;[3]Lanzhou Univ, Sch Clin Med 1, Lanzhou 730000, Peoples R China;[4]Gansu Prov Hosp, Inst Clin Res & Translat Med, Lanzhou, Peoples R China;[5]Second Peoples Hosp Lanzhou City, Dept Cardiovasc Med, Lanzhou, Peoples R China;[6]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Prov Hosp, Dept Cardiovasc Med, 204 Donggang West Rd, Lanzhou 730000, Peoples R China;[3]corresponding author), Lanzhou Univ, Sch Clin Med 1, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：14

期号：4

起止页码：509

外文期刊名：CARDIOVASCULAR DIAGNOSIS AND THERAPY

收录：;Scopus(收录号：2-s2.0-85202467989);WOS:【SCI-EXPANDED(收录号:WOS:001322539900005)】；

基金：This work was supported by grants from the Natural Science Foundation of Gansu Province (No. 22JR5RA665) , the Natural Science Foundation of Gansu Province (No. 20YF3WA011) , the Scientific Research Fund Project of Gansu Provincial Hospital (No. ZX-62000001-2023-274) , and the Innovation and Entrepreneurship Talent Project of Lanzhou (No. 2018-RC-72) .

语种：英文

外文关键词：Radiation-induced heart disease (RIHD); N-acetylcysteine (NAC); mitochondrial oxidative stress; mitochondrial DNA (mtDNA)

摘要：Background: Radiation-induced heart disease (RIHD) is a serious complication of thoracic tumor radiotherapy that substantially affects the quality of life of cancer patients. Oxidative stress plays a pivotal role in the occurrence and progression of RIHD, which prompted our investigation of an innovative approach for treating RIHD using antioxidant therapy. Methods: We used 8-week-old male Sprague-Dawley (SD) rats as experimental animals and H9C2 cells as experimental cells. N-acetylcysteine (NAC) was used as an antioxidant to treat H9C2 cells after X-ray irradiation in this study. In the present study, the extent of cardiomyocyte damage caused by X-ray exposure was determined, alterations in oxidation/antioxidation levels were assessed, and changes in the expression of genes related to mitochondria were examined. The degree of myocardial tissue and cell injury was also determined. Dihydroethidium (DHE) staining, reactive oxygen species (ROS) assays, and glutathione (GSH) and manganese superoxide dismutase (Mn-SOD) assays were used to assess cell oxidation/antioxidation. Flow cytometry was used to determine the mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening. High-throughput transcriptome sequencing and bioinformatics analysis were used to elucidate the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure. Polymerase chain reaction (PCR) was used to verify the expression of differentially expressed genes. Results: X-ray irradiation damaged myocardial tissue and cells, resulting in an imbalance of oxidative and antioxidant substances and mitochondrial damage. NAC treatment increased cell counting kit-8 (CCK-8) levels (P=0.02) and decreased lactate dehydrogenase (LDH) release (P=0.02) in cardiomyocytes. It also reduced the level of ROS (P=0.002) and increased the levels of GSH (P=0.04) and Mn-SOD (P=0.01). The mitochondrial membrane potential was restored (P<0.001), and mPTP opening was inhibited (P<0.001). Transcriptome sequencing and subsequent validation analyses revealed a decrease in the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure, but antioxidant therapy did not reverse the related DNA damage. Conclusions: Antioxidants mitigated radiation-induced myocardial damage to a certain degree, but these agents did not reverse the associated DNA damage. These findings provide a new direction for future investigations by our research group, including exploring the treatment of RIHD-related DNA damage.